Intramuscular Cannabinoids Show a Possible Signal for Acute Pain Relief
A 2020 systematic review and meta-analysis found that cannabinoids produced a small reduction in self-reported acute pain compared with placebo—but the result was driven largely by a single small trial of an intramuscular synthetic THC compound. The findings suggest that how a cannabinoid is administered may matter, while falling well short of establishing injections as an effective treatment for acute pain.
The review published in Cannabis and Cannabinoid Research included six randomized, placebo-controlled trials involving 678 participants. Most participants were experiencing postoperative pain, and the studies tested pharmaceutical cannabinoids rather than commercially available cannabis products. Five trials evaluated orally administered drugs or extracts; one evaluated intramuscular levonantradol, a synthetic THC compound, in 56 people with postoperative, trauma-related, or fracture pain.
Across all 11 treatment comparisons, cannabinoids were associated with a statistically significant improvement in pain scores. However, the evidence was rated low quality because the studies differed substantially in cannabinoid type, dose, timing, follow-up period, and route of administration. The overall result also showed considerable variation between studies.
The route-specific findings were more striking. The five oral trials, which included 622 participants, showed no statistically significant difference from placebo. The single intramuscular trial, involving 56 participants, reported a larger reduction in pain scores with levonantradol. Because this comparison came from just one study—and the injection was not directly compared with an oral cannabinoid in the same trial—it cannot establish that injections are superior to oral treatment.
The apparent difference may be biologically plausible. Oral cannabinoids are absorbed slowly and variably and undergo first-pass metabolism in the liver, which can reduce and delay the amount of drug reaching the bloodstream. An intramuscular injection avoids that digestive and hepatic pathway. Still, pharmacological reasoning does not replace clinical evidence, and the review did not evaluate whether other nonoral formulations would provide the same effect.
Side effects were more common in the cannabinoid groups, particularly nonserious events such as nausea, dizziness, and vomiting. Serious adverse events were uncommon and occurred at similar rates among participants receiving cannabinoids and placebo. That finding is reassuring but should not be interpreted as proof that cannabinoids are broadly safe, since the trials were small and followed participants for relatively short periods.
The review updated the conclusions of a 2017 systematic review, which found no convincing role for cannabinoids in acute pain based on seven trials involving 611 participants. The newer analysis reached a somewhat more favorable statistical result by pooling the available data, but its authors still classified the evidence as low quality.
These results also concern a narrow group of older pharmaceutical compounds and clinical situations, mainly acute postoperative pain. They do not demonstrate that smoking cannabis, using cannabis edibles, or taking over-the-counter CBD products will relieve a new injury or surgical pain. The National Center for Complementary and Integrative Health likewise notes that evidence for cannabinoid-based products varies by condition and formulation, with side effects occurring more often than with placebo in many pain studies.
Larger, well-designed randomized trials are needed to determine whether cannabinoids have a meaningful role in acute pain care, which compounds and doses work best, and whether any benefit outweighs adverse effects. Until that evidence is available, the 2020 findings are best viewed as a signal for further research—not as support for routine synthetic THC injections.
